Aim: The purpose of this research was to compare the cytotoxicity effect of two naturally based intracanal medications, which are silver nanoparticles (AgNPs) and AgNPs with curcumin, to the commonly utilized calcium hydroxide (Ca(OH)(2)). Materials and Methods: Evaluation was done using cell line in vitro. The cell line used in our study was Gingival Fibroblast cells (ATCC PCS-201-012). After 48 h of exposure, the water soluble tetrazolium salt (WST-1) assay was used to assess the vitality of the cells by Abcam kit. Fifty-four samples were categorized randomly into three groups in accordance with the type of intracanal medicament applied: group A-18 samples of AgNPs; group B-18 samples of AgNPs with curcumin; and group C-18 samples of Ca(OH)(2). Each main group was subdivided randomly into six subgroups; three samples for each subgroup according to concentrations (Conc) used, which were 0.01, 0.1, 1, 10, and 100, and normal cells as a control. Statistical analysis was done using Shapiro-Wilk and Kolmogorov-Smirnov tests, paired sample t test, and one-way analysis of variance. Results: In Conc 0.01, the highest viability percentage of living cells with the least cytotoxicity percentage was found in the control group, then in group A, and then in group C, whereas the lowest viability percentage was detected in group B. I the water soluble tetrazolium salt (WST-1) assay was used n Conc 0.1, Conc 1, Conc 10, and Conc 100, the highest viability percentage of living cells was detected in the control group, then in group C, and then in group A; however, the lowest was detected in group B. Conclusion: All three tested intracanal medications were noncytotoxic.